Advertisement

Is VEGF a marker of severity of scrub typhus infection?

  • V. E. Mani
  • P. S. Chauhan
  • J. Kalita
  • S. K. Bhoi
  • U. K. Misra
Original Article
  • 151 Downloads

Abstract

Vascular endothelial growth factor (VEGF) and its receptors have been reported as severity markers of septicemia. Scrub typhus (ST) results in multi-organ dysfunction but the role of VEGF has not been evaluated. We report VEGF and its receptors in ST and its correlation with severity, outcome and laboratory findings. Thirty patients with ST diagnosed by solid phase immune chromatographic assay and Weil–Felix tests were included. Their clinical details, Glasgow Coma Scale (GCS), SOFA and modified Rankin Scale (mRS) scores and laboratory findings were noted. VEGF, VEGFR1 and VEGFR2 were done by ELISA at admission and repeated at 1 month. Outcome was defined at 1 month. Serum VEGF and VEGF-R1 levels were significantly higher and VEGFR2 was significantly lower in the ST patients compared to the controls. These levels significantly improved at 1 month. VEGF level correlated with SOFA score (p = 0.05) and SGPT (p = 0.04). VEGFR1 correlated with hemoglobin (p = 0.04), platelet count (p = 0.03), serum CK (p = 0.001), weakness (p = 0.04) and mRS score (p = 0.04). VEGFR2 did not correlate with any clinical or laboratory parameters. All the patients recovered with doxycycline. Serum VEGF and VEGFR1 levels increased in ST and suggest disease severity but do not predict outcome.

Keywords

Vascular Endothelial Growth Factor Septic Shock Sequential Organ Failure Assessment Vascular Endothelial Growth Factor Level Sequential Organ Failure Assessment Score 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

We thank Mr. Rakesh Kumar Nigam for secretarial help.

Compliance with ethical standards

Ethical approval no

The study was approved by the Institute Ethics Committee (PGI/IP/IEC/52/75/2014).

Funding support

This study was (No. CST/SERPD/D-996) financially supported by a grant from Uttar Pradesh Council of Science & Technology Lucknow, UP, India.

Conflict of interest

There is no conflict of interest to declare.

References

  1. 1.
    Chi WC, Huang JJ, Sung JM, Lan RR, Ko WC, Chen FF (1997) Scrub typhus associated with multiorgan failure: a case report. Scand J Infect Dis 29:634–635CrossRefPubMedGoogle Scholar
  2. 2.
    Seong SY, Choi MS, Kim IS (2001) Orientia tsutsugamushi infection: overview and immune responses. Microbes Infect 3:11–21CrossRefPubMedGoogle Scholar
  3. 3.
    Kim SJ, Chung IK, Chung TS et al (2000) The clinical significance of upper gastrointestinal endoscopy in gastrointestinal vasculitis related to scrub typhus. Endoscopy 32:950–955CrossRefPubMedGoogle Scholar
  4. 4.
    Senger DR, Galli SJ, Dvorak AM, Perruzzi CA, Harvey VS, Dvorak HF (1983) Tumor cells secrete a vascular permeability factor that promotes accumulation of ascites fluid. Science 219:983–985CrossRefPubMedGoogle Scholar
  5. 5.
    Itaya H, Imaizumi T, Yoshida H, Koyama M, Suzuki S, Satoh K (2001) Expression of vascular endothelial growth factor in human monocyte/macrophages stimulated with lipopolysaccharide. Thromb Haemost 85(1):171–176PubMedGoogle Scholar
  6. 6.
    Hoeben A, Landuyt B, Highley MS, Wildiers H, Van Oosterom AT, De Bruijn EA (2004) Vascular endothelial growth factor and angiogenesis. Pharmacol Rev 56(4):549–580CrossRefPubMedGoogle Scholar
  7. 7.
    Mankhambo LA, Banda DL, IPD Study Group et al (2010) The role of angiogenic factors in predicting clinical outcome in severe bacterial infection in Malawian children. Crit Care 14:R91PubMedCentralCrossRefPubMedGoogle Scholar
  8. 8.
    Maroeska Te Loo D, Bosma N, Van Hinsbergh V et al (2004) Elevated levels of vascular endothelial growth factor in serum of patients with D+ HUS. Pediatr Nephrol 19(7):754–760CrossRefPubMedGoogle Scholar
  9. 9.
    Medana IM, Day NP, Roberts R et al (2010) Induction of the vascular endothelial growth factor pathway in the brain of adults with fatal falciparum malaria is a non-specific response to severe disease. Histopathology 57(2):282–294PubMedCentralCrossRefPubMedGoogle Scholar
  10. 10.
    Misra UK, Kalita J, Singh AP (2014) Role of vascular endothelial growth factor (VEGF) in the neurological manifestations of dengue: a preliminary study. Inflammation 37(2):611–614CrossRefPubMedGoogle Scholar
  11. 11.
    Tseng CS, Lo HW, Teng HC, Lo WC, Ker CG (2005) Elevated levels of plasma VEGF in patients with dengue hemorrhagic fever. FEMS Immunol Med Microbiol 43:99–102CrossRefPubMedGoogle Scholar
  12. 12.
    Srikiatkhachorn A, Ajariyakhajorn C, Endy TP et al (2007) Virus-induced decline in soluble vascular endothelial growth receptor 2 is associated with plasma leakage in dengue hemorrhagic fever. J Virol 81:1592–1600PubMedCentralCrossRefPubMedGoogle Scholar
  13. 13.
    Misra UK, Kalita J, Roy AK, Mandal SK, Srivastava M (2000) Role of clinical, radiological, and neurophysiological changes in predicting the outcome of tuberculous meningitis: a multivariable analysis. J Neurol Neurosurg Psychiatry 68(3):300–303PubMedCentralCrossRefPubMedGoogle Scholar
  14. 14.
    Resto-Ruiz SI, Schmiederer M, Sweger D et al (2002) Induction of a potential paracrine angiogenic loop between human THP-1 macrophages and human microvascular endothelial cells during Bartonella henselae infection. Infect Immun 70(8):4564–4570PubMedCentralCrossRefPubMedGoogle Scholar
  15. 15.
    Savory LJ, Stacker SA, Fleming SB, Niven BE, Mercer AA (2000) Viral vascular endothelial growth factor plays a critical role in orf virus infection. J Virol 74(22):10699–10706PubMedCentralCrossRefPubMedGoogle Scholar
  16. 16.
    Pickkers P, Sprong T, Lv E, Hoeven HV, Smits P, Deuren MV (2005) Vascular endothelial growth factor is increased during the first 48 hours of human septic shock and correlates with vascular permeability. Shock 24(6):508–512CrossRefPubMedGoogle Scholar
  17. 17.
    Shapiro NI, Yano K, Okada H et al (2008) A prospective, observational study of soluble FLT-1 and vascular endothelial growth factor in sepsis. Shock 29:452–457CrossRefPubMedGoogle Scholar
  18. 18.
    Alves BE, Montalvao SA, Aranha FJ et al (2011) Time-course of sFlt-1 and VEGF-A release in neutropenic patients with sepsis and septic shock: a prospective study. J Transl Med 9:23PubMedCentralCrossRefPubMedGoogle Scholar
  19. 19.
    Yang KY, Liu KT, Chen YC et al (2011) Plasma soluble vascular endothelial growth factor receptor-1 levels predict outcomes of pneumonia-related septic shock patients: a prospective observational study. Crit Care 15(1):R11PubMedCentralCrossRefPubMedGoogle Scholar
  20. 20.
    Van der Flier M, van Leeuwen HJ, van Kessel KP, Kimpen JL, Hoepelman AI, Geelen SP (2005) Plasma vascular endothelial growth factor in severe sepsis. Shock 23:35–38CrossRefPubMedGoogle Scholar
  21. 21.
    Karlsson S, Pettilä V, Tenhunen J, Lund V, Hovilehto S, Ruokonen E, Finnsepsis Study Group (2008) Vascular endothelial growth factor in severe sepsis and septic shock. Anesth Analg 106:1820–1826CrossRefPubMedGoogle Scholar
  22. 22.
    Puca R, Nardinocchi L, D’Orazi G (2008) Regulation of vascular endothelial growth factor expression by homeodomain-interacting protein kinase-2. J Exp Clin Cancer Res 27:22PubMedCentralCrossRefPubMedGoogle Scholar
  23. 23.
    Kumpers P, van Meurs M, David S et al (2009) Time course of angiopoietin-2 release during experimental human endotoxemia and sepsis. Crit Care 13:R64PubMedCentralCrossRefPubMedGoogle Scholar
  24. 24.
    Siner JM, Bhandari V, Engle KM, Elias JA, Siegel MD (2009) Elevated serum angiopoietin 2 levels are associated with increased mortality in sepsis. Shock 31:348–353CrossRefPubMedGoogle Scholar
  25. 25.
    Kim DM, Kim SW, Choi SH et al (2010) Clinical and laboratory findings associated with severe scrub typhus. BMC Infect Dis 10:108PubMedCentralCrossRefPubMedGoogle Scholar
  26. 26.
    Issac R, Varghese GM, Mathai E et al (2004) Scrub typhus: prevalence and diagnostic issues in rural Southern India. Clin Infect Dis 39:1395–1396CrossRefGoogle Scholar
  27. 27.
    Prakash JA, Abraham OC, Mathai E (2006) Evaluation of tests for serological diagnosis of scrub typhus. Trop Dr 36:212–213CrossRefGoogle Scholar
  28. 28.
    Lee KD, Moon C, Oh WS, Sohn KM, Kim BN (2014) Diagnosis of scrub typhus: introduction of the immunochromatographic test in Korea. Korean J Intern Med 29(2):253–255PubMedCentralCrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • V. E. Mani
    • 1
  • P. S. Chauhan
    • 1
  • J. Kalita
    • 1
  • S. K. Bhoi
    • 1
  • U. K. Misra
    • 1
  1. 1.Department of NeurologySanjay Gandhi Post Graduate Institute of Medical SciencesLucknowIndia

Personalised recommendations